TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16290	49093;49094;49095	chr2:178614646;178614645;178614644	chr2:179479373;179479372;179479371
N2AB	14649	44170;44171;44172	chr2:178614646;178614645;178614644	chr2:179479373;179479372;179479371
N2A	13722	41389;41390;41391	chr2:178614646;178614645;178614644	chr2:179479373;179479372;179479371
N2B	7225	21898;21899;21900	chr2:178614646;178614645;178614644	chr2:179479373;179479372;179479371
Novex-1	7350	22273;22274;22275	chr2:178614646;178614645;178614644	chr2:179479373;179479372;179479371
Novex-2	7417	22474;22475;22476	chr2:178614646;178614645;178614644	chr2:179479373;179479372;179479371
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-110
• Domain position: 29
• Structural Position: 46
• Q(SASA): 0.1916
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
I/V	rs778793317	-1.251	0.001	N	0.224	0.054	0.269558022972	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	5.65E-05	None	0	None	0	1.79E-05	0
I/V	rs778793317	-1.251	0.001	N	0.224	0.054	0.269558022972	gnomAD-4.0.0	7.97067E-06	None	None	None	None	I	None	0	0	None	0	2.79049E-05	None	0	0	1.14509E-05	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
I/A	0.8996	likely_pathogenic	0.8592	pathogenic	-1.915	Destabilizing	0.415	N	0.733	prob.delet.	None	None	None	None	I
I/C	0.8858	likely_pathogenic	0.8605	pathogenic	-0.939	Destabilizing	0.989	D	0.787	deleterious	None	None	None	None	I
I/D	0.9957	likely_pathogenic	0.9926	pathogenic	-1.545	Destabilizing	0.987	D	0.881	deleterious	None	None	None	None	I
I/E	0.9831	likely_pathogenic	0.9734	pathogenic	-1.493	Destabilizing	0.961	D	0.867	deleterious	None	None	None	None	I
I/F	0.6663	likely_pathogenic	0.6068	pathogenic	-1.297	Destabilizing	0.923	D	0.73	prob.delet.	None	None	None	None	I
I/G	0.9843	likely_pathogenic	0.9756	pathogenic	-2.299	Highly Destabilizing	0.961	D	0.857	deleterious	None	None	None	None	I
I/H	0.979	likely_pathogenic	0.965	pathogenic	-1.642	Destabilizing	0.996	D	0.871	deleterious	None	None	None	None	I
I/K	0.9482	likely_pathogenic	0.9065	pathogenic	-1.362	Destabilizing	0.949	D	0.867	deleterious	D	0.676885921	None	None	I
I/L	0.3709	ambiguous	0.3345	benign	-0.899	Destabilizing	0.19	N	0.377	neutral	N	0.521138727	None	None	I
I/M	0.2909	likely_benign	0.2564	benign	-0.578	Destabilizing	0.901	D	0.706	prob.neutral	D	0.660160948	None	None	I
I/N	0.924	likely_pathogenic	0.8825	pathogenic	-1.182	Destabilizing	0.987	D	0.881	deleterious	None	None	None	None	I
I/P	0.9787	likely_pathogenic	0.9698	pathogenic	-1.209	Destabilizing	0.987	D	0.883	deleterious	None	None	None	None	I
I/Q	0.9601	likely_pathogenic	0.9342	pathogenic	-1.292	Destabilizing	0.987	D	0.872	deleterious	None	None	None	None	I
I/R	0.943	likely_pathogenic	0.895	pathogenic	-0.838	Destabilizing	0.949	D	0.878	deleterious	D	0.73581048	None	None	I
I/S	0.9331	likely_pathogenic	0.8979	pathogenic	-1.787	Destabilizing	0.923	D	0.849	deleterious	None	None	None	None	I
I/T	0.8459	likely_pathogenic	0.7711	pathogenic	-1.615	Destabilizing	0.722	D	0.731	prob.delet.	D	0.605996502	None	None	I
I/V	0.1118	likely_benign	0.1042	benign	-1.209	Destabilizing	0.001	N	0.224	neutral	N	0.431349076	None	None	I
I/W	0.9839	likely_pathogenic	0.9776	pathogenic	-1.486	Destabilizing	0.996	D	0.859	deleterious	None	None	None	None	I
I/Y	0.9289	likely_pathogenic	0.9006	pathogenic	-1.248	Destabilizing	0.961	D	0.795	deleterious	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.